Sint-Martens-Lennik, Belgium
Sint-Martens-Lennik, Belgium

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Hiemstra T.F.,University of Cambridge | Walsh M.,McMaster University | Mahr A.,University of Paris Descartes | Savage C.O.,University of Birmingham | And 9 more authors.
JAMA - Journal of the American Medical Association | Year: 2010

Context: Current remission maintenance therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are limited by partial efficacy and toxicity. Objective: To compare the effects of mycophenolate mofetil with azathioprine on the prevention of relapses in patients with AAV. Design, Setting, and Participants: Open-label randomized controlled trial, International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides (IMPROVE), to test the hypothesis that mycophenolate mofetil is more effective than azathioprine for preventing relapses in AAV. The trial was conducted at 42 centers in 11 European countries between April 2002 and January 2009 (42-month study). Eligible patients had newly diagnosed AAV (Wegener granulomatosis or microscopic polyangiitis) and were aged 18 to 75 years at diagnosis. Interventions: Patients were randomly assigned to azathioprine (starting at 2 mg/kg/d) or mycophenolate mofetil (starting at 2000 mg/d) after induction of remission with cyclophosphamide and prednisolone. Main Outcome Measures: The primary end point was relapse-free survival, which was assessed using a Cox proportional hazards model. The secondary end points were Vasculitis Damage Index, estimated glomerular filtration rate, and proteinuria. Results: A total of 156 patients were assigned to azathioprine (n = 80) or mycophenolate mofetil (n = 76) and were followed up for a median of 39 months (interquartile range, 0.66-53.6 months). All patients were retained in the analysis by intention to treat. Relapses were more common in the mycophenolate mofetil group (42/76 patients) compared with the azathioprine group (30/80 patients), with an unadjusted hazard ratio (HR) for mycophenolate mofetil of 1.69 (95% confidence interval [CI], 1.06-2.70; P = .03). Severe adverse events did not differ significantly between groups. There were 22 severe adverse events in 13 patients (16%) in the azathioprine group and there were 8 severe adverse events in 8 patients (7.5%) in the mycophenolate mofetil group (HR, 0.53 [95% CI, 0.23-1.18]; P = .12). The secondary outcomes of Vasculitis Damage Index, estimated glomerular filtration rate, and proteinuria did not differ significantly between groups. Conclusions: Among patients with AAV, mycophenolate mofetil was less effective than azathioprine for maintaining disease remission. Both treatments had similar adverse event rates. Trial Registration: clinicaltrials.gov Identifier: NCT00307645 ©2010 American Medical Association. All rights reserved.


Tack D.,EpiCURA Hospital | Jahnen A.,CRP Henri Tudor | Kohler S.,CRP Henri Tudor | Harpes N.,Ministry of Health | And 3 more authors.
European Radiology | Year: 2014

Objective: To report short- and long-term effects of an audit process intended to optimise the radiation dose from multi-detector row computed tomography (MDCT). Methods: A survey of radiation dose from all eight MDCT departments in the state of Luxembourg performed in 2007 served as baseline, and involved the most frequently imaged regions (head, sinus, cervical spine, thorax, abdomen, and lumbar spine). CT dose index volume (CTDIvol), dose-length product per acquisition (DLP/acq), and DLP per examination (DLP/exa) were recorded, and their mean, median, 25th and 75th percentiles compared. In 2008, an audit conducted in each department helped to optimise doses. In 2009 and 2010, two further surveys evaluated the audit's impact on the dose delivered. Results: Between 2007 and 2009, DLP/exa significantly decreased by 32-69% for all regions (P <0.001) except the lumbar spine (5%, P =0.455). Between 2009 and 2010, DLP/exa significantly decreased by 13-18% for sinus, cervical and lumbar spine (P ranging from 0.016 to less than 0.001). Between 2007 and 2010, DLP/exa significantly decreased for all regions (18-75%, P <0.001). Collective dose decreased by 30% and the 75th percentile (diagnostic reference level, DRL) by 20-78%. Conclusions: The audit process resulted in long-lasting dose reduction, with DRLs reduced by 20 -78%, mean DLP/examination by 18-75%, and collective dose by 30%. Key points: • External support through clinical audit may optimise default parameters of routine CT. • Reduction of 75th percentiles used as reference diagnostic levels is 18 -75%. • The effect of this audit is sustainable over time. • Dose savings through optimisation can be added to those achievable through CT. © European Society of Radiology 2013.


Hatzimouratidis K.,Aristotle University of Thessaloniki | Eardley I.,University of Leeds | Giuliano F.,Service dUrologie | Hatzichristou D.,Aristotle University of Thessaloniki | And 4 more authors.
European Urology | Year: 2012

Context: Penile curvature can be congenital or acquired. Acquired curvature is secondary due to La Peyronie (Peyronie's) disease. Objective: To provide clinical guidelines on the diagnosis and treatment of penile curvature. Evidence acquisition: A systematic literature search on the epidemiology, diagnosis, and treatment of penile curvature was performed. Articles with the highest evidence available were selected and formed the basis for assigning levels of evidence and grades of recommendations. Evidence synthesis: The pathogenesis of congenital penile curvature is unknown. Peyronie's disease is a poorly understood connective tissue disorder most commonly attributed to repetitive microvascular injury or trauma during intercourse. Diagnosis is based on medical and sexual histories, which are sufficient to establish the diagnosis. Physical examination includes assessment of palpable nodules and penile length. Curvature is best documented by a self-photograph or pharmacologically induced erection. The only treatment option for congenital penile curvature is surgery based on plication techniques. Conservative treatment for Peyronie's disease is associated with poor outcomes. Pharmacotherapy includes oral potassium para-aminobenzoate, intralesional treatment with verapamil, clostridial collagenase or interferon, topical verapamil gel, and iontophoresis with verapamil and dexamethasone. They can be efficacious in some patients, but none of these options carry a grade A recommendation. Steroids, vitamin E, and tamoxifen cannot be recommended. Extracorporeal shock wave treatment and penile traction devices may only be used to treat penile pain and reduce penile deformity, respectively. Surgery is indicated when Peyronie's disease is stable for at least 3 mo. Tunical shortening procedures, especially plication techniques, are the first treatment options. Tunical lengthening procedures are preferred in more severe curvatures or in complex deformities. Penile prosthesis implantation is recommended in patients with erectile dysfunction not responding to pharmacotherapy. Conclusions: These European Association of Urology (EAU) guidelines summarise the present information on penile curvature. The extended version of the guidelines is available on the EAU Web site (www.uroweb.org/guidelines/). © 2012 European Association of Urology.


Vermijlen D.,Free University of Colombia | Brouwer M.,Free University of Colombia | Donner C.,Hopital Erasme | Liesnard C.,Hopital Erasme | And 6 more authors.
Journal of Experimental Medicine | Year: 2010

The fetus and infant are highly susceptible to viral infections. Several viruses, including human cytomegalovirus (CMV), cause more severe disease in early life compared with later life. It is generally accepted that this is a result of the immaturity of the immune system. γδ T cells are unconventional T cells that can react rapidly upon activation and show major histocompatibility complex-unrestricted activity. We show that upon CMV infection in utero, fetal γδ T cells expand and become differentiated. The expansion was restricted to Vγ9-negative γδ T cells, irrespective of their Vδ chain expression. Differentiated γδ T cells expressed high levels of IFN-γ, transcription factors T-bet and eomes, natural killer receptors, and cytotoxic mediators. CMV infection induced a striking enrichment of a public Vγ8Vδ1-TCR, containing the germline-encoded complementary- determining-region-3 (CDR3) δ1-CALGELGDDKLIF/CDR3γ8-CATWDTTGWFKIF. Public Vγ8Vδ1-TCR-expressing cell clones produced IFN-γ upon coincubation with CMV-infected target cells in a TCR/CD3-dependent manner and showed antiviral activity. Differentiated γζ T cells and public Vγ8Vδ1-TCR were detected as early as after 21 wk of gestation. Our results indicate that functional fetal γδ T cell responses can be generated during development in utero and suggest that this T cell subset could participate in antiviral defense in early life. © 2010 Vermijlen et al.


Topal B.,Catholic University of Leuven | Aerts R.,Catholic University of Leuven | Weerts J.,Cliniques Saint Joseph Liege | Feryn T.,AZ Sint Jan Bruges | And 5 more authors.
The Lancet Oncology | Year: 2013

Background: Postoperative pancreatic fistula is the leading cause of death and morbidity after pancreaticoduodenectomy. However, the best reconstruction method to reduce occurrence of fistula is debated. We did a multicentre, randomised superiority trial to compare the outcomes of different reconstructive techniques in patients undergoing pancreaticoduodenectomy for pancreatic or periampullary tumours. Methods: Patients aged 18-85 years with confirmed or suspected neoplasms of the pancreas, distal bile duct, ampulla vateri, duodenum, or periampullary tumours were eligible for inclusion. An internet-based platform was used to randomly assign patients to either pancreaticojejunostomy or pancreaticogastrostomy as reconstruction after pancreaticoduodenectomy, using permuted blocks with six patients per block. Within each centre the randomisation was stratified on the pancreatic duct diameter (≤3 mm vs >3 mm) measured at the time of surgery. The primary endpoint was the occurrence of clinical postoperative pancreatic fistula (grade B or C) as defined by the International Study Group on Pancreatic Fistula. The study was not masked and analyses were done by intention to treat. Patient follow-up was closed 2 months after discharge from the hospital. This study is registered with ClinicalTrials.gov, number NCT00830778. Findings: Between June, 2009, and August, 2012, we randomly allocated 167 patients to receive pancreaticojejunostomy and 162 to receive pancreaticogastrostomy. 33 (19·8%) patients in the pancreaticojejunostomy group and 13 (8·0%) in the pancreaticogastrostomy group had clinical postoperative pancreatic fistula (OR 2·86, 95% CI 1·38-6·17; p=0·002). The overall incidence of postoperative complications did not differ significantly between the groups (99 in the pancreaticojejunostomy group vs 100 in the pancreaticogastrostomy group), although more events in the pancreaticojejunostomy group were of grade ≥3a than in the pancreaticogastrostomy group (39 vs 35). Interpretation: In patients undergoing pancreaticoduodenectomy for pancreatic head or periampullary tumours, pancreaticogastrostomy is more efficient than pancreaticojejunostomy in reducing the incidence of postoperative pancreatic fistula. Funding: Funding Johnson & Johnson Medical Devices, Belgium. © 2013 Elsevier Ltd.


Pepersack T.,Hopital Erasme
Revue Medicale de Bruxelles | Year: 2010

Most people in contemporary western society die of the chronic diseases of old age. Whilst palliative care is appropriate for elderly patients with chronic, non-malignant disease, few of these patients access such care compared with cancer patients. That patients dying with dementia have significant health care needs, comparable with cancer patients, is now well established. Yet, their families typically describe poor advance-care planning and an inadequate level of symptom control, with distress associated with pain, pressure sores, constipation, restlessness and shortness of breath. A comparison of people dying with advanced dementia or terminal cancer found that those with dementia were more likely to experience burdensome interventions and restraints and to have had poor advance-care planning. Prognostic models that attempt to estimate survival of > 6 months in demented patients have generally poor discrimination, reflecting the unpredictable nature of most non-malignant disease. However, a number of generic and disease-specific predictor variables were identified that may help clinicians identify older, non-cancer patients with poor prognoses and palliative care needs. Simple, well-validated prognostic models that provide clinicians with objective measures of palliative status in demented patients are needed. Additionally, research that analyses the effect of comprehensive geriatric assessment and geriatric palliative care on psychosocial outcomes in demented patients and their caregivers is needed. Advances care planning and directives making before death allow meeting patient's preferences.


Evrard L.,Hopital Erasme
Bulletin du Groupèment international pour la recherche scientifique en stomatologie & odontologie | Year: 2010

Oral allergies represent a pathological entity not well known nor diagnosed by dental health professionals. The purpose of this work is to present an information relative to the multidisciplinary steps to be done to solve allergy problems. Three clinical examples of contact oral allergies (to mercury, or gold, or methacrylates) are presented, as to illustrate signs and symptoms of an oral allergy to the more frequent dental materials implied.We discuss the problem of oral allergies from what is known from the scientific literature. We stress the importance of a multidisciplinary approach to take into account patients with an oral allergy, with participation of specialists from dental and dermatologic fields.


As the prevalence of obesity increases worldwide, clinicians will be more and more frequently confronted with obese, critically ill patients. Optimal administration of antibiotics is already a challenge in the critically ill patient because pharmacokinetics (PK) of antibiotics is often altered, and infections are more frequently caused by resistant pathogens than in the non-critically ill patient. Obesity per se may further alter the PK of antibiotics. This paper provides a narrative review of the potential PK changes of antibiotics in the obese, critically ill patient, and recommendations for optimal antibiotic therapy for the most frequently used antibiotics. However, these recommendations are essentially based on small sample-sized PK studies with no evaluation of outcome, and thus must be considered with caution. On one hand, critically ill patients may need higher than recommended regimens of β-lactams, linezolid, moxifloxacin, levofloxacin, tigecycline, and colistin; however, no further dose adjustment is necessary in obese, septic patients. Increased dosage regimens of β-lactams may be necessary only to treat obese, non-critically ill patients. On the opposite, dosage regimens should be based on total body weight for amikacin in patients with a body mass index (BMI) between 20 and 40 kg/m2, vancomycin, and daptomycin, and on adjusted body weight for ciprofloxacin, gentamycin, tobramycin, and amikacin in patients with a BMI greater than 40 kg/m2. Because of the lack of PK studies in this special patient population, and the large inter- and intraindividual PK drug variability in critically ill patients, we recommend therapeutic drug monitoring of all antibiotics administered, whenever possible, to optimize drug therapy. © 2015, Société de réanimation de langue française (SRLF) and Springer-Verlag France.


Wolff F.,HOpital Erasme | Deleers M.,HOpital Erasme | Melot C.,Free University of Colombia | Gulbis B.,HOpital Erasme | Cotton F.,HOpital Erasme
Clinica Chimica Acta | Year: 2013

A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was developed for reliably quantifying hepcidin-25 in human urine and serum. A 95% reference range was established for serum hepcidin-25 levels by standardizing the sampling time between 8:00. am and 11:00. am in 90 apparently healthy volunteers. The association between hepcidin-25 concentration and other biological parameters was studied using multivariable analysis and the coefficient of renal excretion of hepcidin-25 was calculated. Preanalytical variables were also investigated.The LC-MS/MS method was validated using a recent validation strategy based on accuracy profiles. Good results were obtained in terms of trueness, precision, and linearity in the following dosing ranges: from 0.77 to 200. nmol/L for urine and from 0.48 to 100. nmol/L for serum. The 95% reference range of serum hepcidin-25 concentration established after excluding known conditions that affect hepcidin-25 expression was 1.5 to 15.2. nmol/L. A difference between genders was demonstrated with a median concentration of 5.5 versus 7.2. nmol/L for women and men, respectively. Serum hepcidin-25 concentrations were strongly correlated with ferritin and, to a lesser extent, with iron levels. The coefficient of renal excretion ranged from 0.1 to 16.4%. Higher values of hepcidin-25 concentrations were observed on ethylene diamine tetraacetate tubes compared to serum or lithium-heparin devices. © 2013 Elsevier B.V.


Pandolfo M.,Hopital Erasme
CONTINUUM Lifelong Learning in Neurology | Year: 2013

PURPOSE OF REVIEW: Ataxia is the predominant manifestation of many acquired and inherited neurologic disorders affecting the cerebellum, its connections, and the afferent proprioceptive pathways. This article reviews the phenomenology and etiologies of cerebellar and afferent ataxias and provides indications for a rational approach to diagnosis and management. RECENT FINDINGS: The pathophysiology of ataxia is being progressively understood and linked to the functional organization of the cerebellum. The impact of cerebellar diseases on different neurologic functions has been better defined and shown not to be limited to loss of motor coordination. The role of autoimmunity is increasingly recognized as a cause of sporadic cases of ataxia. Large collaborative studies of long duration are providing crucial information on the clinical spectrum and natural history of both sporadic ataxias (such as the cerebellar form of multiple system atrophy) and inherited ataxias. New dominant and recessive ataxia genes have been identified. On the therapeutic front, progress mostly concerns the development of treatments for Friedreich ataxia. SUMMARY: Ataxia is the clinical manifestation of a wide range of disorders. In addition to accurate clinical assessment, MRI plays a major role in the diagnostic workup, allowing us to distinguish degenerative conditions from those due to other types of structural damage to the cerebellar or proprioceptive systems. Diagnostic algorithms based on clinical features, imaging, and neurophysiologic and biochemical parameters can be used to guide genetic testing for hereditary ataxias, the diagnosis of which is likely to be greatly improved by the introduction of new-generation DNA-sequencing approaches. Some rare forms of ataxia can be treated, so their diagnosis should not be missed. Proven symptomatic treatments for ataxia are still lacking, but intensive physical therapy appears to be helpful. Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

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